Blood. PowerPoint Lecture Presentations prepared by Jason LaPres

Transcription

1 19 Blood NOTE: Presentations extensively modi6ied for use in MCB 244 & 246 at the University of Illinois by Drs. Kwast & Brown ( ) PowerPoint Lecture Presentations prepared by Jason LaPres Lone Star College North Harris

2 Chapter 19 Learning Objectives 1. Describe the components and major functions of blood. 2. Describe the composition and function of plasma. 3. List the characteristics and functions of erythrocytes, including hemoglobin, and describe erythrocyte formation (erythropoiesis) and recycling. 4. Explain the basis of blood typing and histocompatibility. 5. Describe the structure/function of white blood cells and their formation. 6. Describe the structure/function of platelets. 7. Describe the mechanisms involved in blood clot formation. 2

3 Introduction to the Cardiovascular System Cardiovascular System = blood, heart & blood vessels Circulatory System = cardiovascular & lymphatic systems Blood a fluid connective tissue with matrix (plasma) and formed elements (cells) involved in: 1. Transport of dissolved substances (gases, nutrients, hormones, wastes) 2. Regulation of ph and ion composition 3. Restriction of fluid losses at injury sites (clotting) 4. Defense against toxins and pathogens (leukocytes) 5. Stabilization of body temperature 3

4 19-1 Physical Characteristics of Blood Medial cubital vein Fig ph = 7.4 Temp. = 38ºC Vol. = 4-6 liters (~7% body wt.) High Viscosity Fractionate Hemopoiesis: Hemocytoblasts myeloid & lymphoid stem cells 4

5 19-1 Physical Characteristics of Blood: Plasma 5

6 19-1 Physical Characteristics of Blood: Formed Elements 6

7 19-2 Blood Fractions: Plasma Makes up 50 60% of blood volume More than 90% of plasma is water Plasma and Interstitial Fluid are both extracellular fluids: exchange H 2 O, ions and small solutes (no protein) across the capillary wall Composition of plasma and interstitial fluid differ in terms of Levels of O 2 and CO 2 Concentrations and types of dissolved proteins 7

8 19-2 Blood Fractions: Plasma Proteins Albumins (60%) Transport substances such as fatty acids, thyroid hormones, and steroid hormones; made by liver; major contributor to plasma osmotic pressure Globulins (35%) Antibodies, also called immunoglobulins Transport globulins (small molecules): hormone-binding proteins, metalloproteins, apolipoproteins (lipoproteins), & steroid-binding proteins Fibrinogen (4%) Molecules that form clots and produce long, insoluble strands of fibrin After soluble fibrinogen is turned into solid fibrin, remaining liquid = serum. Other Plasma Proteins (1%) Enzymes, hormones, prohormones: Composition fluctuates Origin of Plasma Proteins: 90% liver; Antibodies plasma cells; Peptide hormones endocrine 8

9 19-3 Blood Fractions: Red Blood Cells Red blood cells (RBCs): 99.9% of formed elements in blood Hemoglobin The red pigment that gives whole blood its color Binds and transports oxygen (and carbon dioxide) Red blood cell count: the number of RBCs in 1 microliter of whole blood Male: million; Female: million Hematocrit (HCT or Ht) (packed cell volume [PCV] also used): percentage of RBCs in centrifuged whole blood Male: 40 54; Female:

10 19-3 Blood Fractions: Red Blood Cells Erythrocyte Structure biconcave disc High surface-to-volume ratio Quickly absorbs and releases oxygen Discs form stacks called rouleaux Smooth the flow through narrow vessels Discs bend and flex to enter small capillaries: 7.8 µm RBC passes through 4 µm capillary Figure Figure 19 2d

11 19-3 Blood Fractions: Red Blood Cells Lack organelles including nuclei, mitochondria & ribosomes No cell division or repair possible Anaerobic metabolism only (no mitochondria) Why so??? Live ~ 120 days Cell is 97% hemoglobin (Hb) ~280 million Hb/RBC, 4 O 2 binding heme/hb = >1 billion O 2 / RBC x 25 trillion RBCs/indiv. = > 25 x O 2 /indiv.! 1/3 of all cells (25 trillion out of 75 trillion) are RBCs! Normal hemoglobin g/dl whole blood 11

12 19-3 Blood Fractions: Red Blood Cells Hemoglobin Structure/Function Complex quaternary structure 2 α chains & 2 β chains: Each chain has 1 molecule of heme with O 2 binding iron Oxyhemoglobin (O 2 bound, bright red) Deoxyhemoglobin (no O 2, burgundy) 98.5% of O 2 is carried by Hb compared to 20% of CO 2 ; the latter is bound to amino acids on α and β chains, NOT heme called carbaminohemoglobin At peripheral capillaries, low plasma O 2 leads to release of O 2 and binding of CO 2 At lungs, opposite occurs - O 2 loaded and CO 2 expelled 12 Figure 19 3

13 19-3 Blood Fractions: Red Blood Cells Hemoglobin Oxygen Dissociation Curves Comparison of Fetal vs. Adult Hb and Effects of ph, temp and di- (or bis-) phosphoglycerate (DPG or BPG) (Expression can be induced by Hydroxyurea or, Butyrate) Fig

14 19-3 Blood Fractions: Red Blood Cells Hemoglobin Disorders: Anemia = O 2 starvation due to: 1. Insufficient numbers of erythrocytes 2. Low hemoglobin 3. Abnormal hemoglobin: Thalassemia: an autosomal recessive mutation (Mediterranean origin) that results in the inability to produce sufficient α or β chains slow RBC production and fragile & short-lived cells; periodic blood transfusions may be necessary; mutation thought to protect against malaria (same for sickle-cell). Sickle-Cell Anemia: an autosomal recessive mutation in a single amino acid of β chain (sub-saharan origin) When Hb highly oxygenated, cells have normal shape When Hb O 2 low, adjacent Hbs interact and RBCs deform into crescent shape: cells become fragile and block capillaries 14

15 19-3 Blood Fractions: Red Blood Cell Turnover RBCs live for ca. 120 days (travel 700 miles!) 1% of circulating RBCs wear out every day (lack repair mechanisms) That s about 3 million RBCs/second! Macrophages of liver, spleen and bone marrow monitor RBCs and engulf before membranes rupture (hemolyze) Phagocytes break hemoglobin into constitutive components: Globular proteins into amino acids; heme to biliverdin & iron Transferrin, a plasma protein, transports iron back to bone marrow for new RBCs; excess transferrins removed by liver and spleen and iron stored as ferritin or hemosiderin If excess hemoglobin breakdown, products can appear in urine; Hemoglobinuria If whole red blood cells appear in urine, signals kidney or urinary tract damage; Hematuria 15

16 19-3 Blood Fractions: Red Blood Cell Turnover Biliverdin (green) is converted to bilirubin (yellow) and is released into blood, filtered by liver, and excreted in bile Jaundice = failure of bilirubin to be excreted in bile, collects in peripheral tissues yellow skin & eyes In gut, bilirubin urobilins (yellow) & stercobilins (brown) via intestinal bacteria Urobilins absorbed or excreted in urine (hence yellow color to urine) Stercobilins remain in feces (hence brown color) 16

17 19-3 Blood Fractions: Red Blood Cell Turnover Fig 19 5 Recycling of Red Blood Cell Components 17

18 19-3 Blood Fractions: Red Blood Cell Formation Fig 19 6 Erythropoiesis (RBC Formation) In adults, occurs only in myeloid tissue (red bone marrow): 1. Hemocytoblasts differentiates into myeloid stem cells 2. Myeloid stem cells undergo multiple stages of differentiation 3. Cells fill with Hb, lose organelles (nucleus too) 4. After ~ 5 days, reticulocytes are formed (Hb + some ribosomes); remain in bone marrow for 2 days and then released into blood, where they account for 0.8% of total blood RBCs 5. After ~ 24h in circulation, reticulocytes lose ribosomes (lose protein synthesis capacity) and mature into erythrocytes Vitamin B 12, B 6 and folic acid necessary for stem cell division Destruction of gastric parietal cells can lead to loss of intrinsic factor, which is required for B 12 absorption, and can lead to pernicious anemia 18

19 19-3 Blood Fractions: Red Blood Cell Formation Stimulating Hormones Erythropoietin (EPO): hormone, released by kidney during hypoxia (low O 2, e.g., high altitude or disease), anemia, ischemia, etc. Stimulates RBC Production by: cell division rates (10x; ~30 million cells/s) Hb synthesis = maturation time Blood Doping = infusing additional RBCs to increase O 2 carrying capacity and, thus, enhance endurance performance; may also be produced by EPO injections: O 2 to tissues, but also hematocrit/viscosity clots, stroke, heart strain, kidney failure 19

20 19-3 Blood Doping & Lance Armstrong s Story 20

21 19-3 Blood Fractions: Red Blood Cell Tests 21

22 19-4 Blood Typing All cell membranes have surface antigens: indicate self (antigen = substance that triggers immune response) RBCs have 50+ surface antigens (e.g., glycoproteins or glycolipids) of which 3 are very important for blood transfusion: agglutinogens A, B, Rh (D) Blood types: A, B, AB or O genetically determined by presence or absence of surface antigens (A, B & Rh) Rh + = antigen Rh (85%); Rh - = none (15%) At birth, blood contains antibodies against A and/or B antigens; however, this is not true for Rh as only sensitized individuals have antibodies to Rh (D) 4% 40% 10% 46% 22

23 Table 19-2 Differences in Blood Group Distribution 23

24 19-4 Blood Typing Transfusion Cross-Reactions Plasma antibody meets specific surface antigen Blood will agglutinate and hemolyze Occurs if donor and recipient blood are not compatible O - = universal donor (AB = universal recipient ) Cross-Match Testing: tests for other antigens by reacting donors RBCs to recipients plasma Fig 19-7 Fig 19 8 Blood Type Test Anti-D + = Rh + 24

25 19-4 Blood Typing: Rh antibodies Figure 19 9 Antibodies against Rh (D) antigen only form upon exposure and they are small enough to cross placenta (unlike anti-a and anti-b antibodies) Hemolytic disease of newborn/erythroblastosis fetalis: Rh - mom pregnant with Rh + baby, gets exposed to D antigen during birth, makes anti-d antibodies. Pregnant with second Rh + baby, her antibodies cross placenta, causing agglutination and lysis of fetal RBCs anemia and death - fetal transfusion may be given and/or early delivery Easily prevented if known: Treat mom with RhoGam (anti-rh antibodies) during last 3 months of her first Rh + pregnancy: prevents antibody formation in the first place. 25

26 19-5 Blood Fractions: White Blood Cells Leukocytes (5 types) Have nuclei & organelles but no hemoglobin (hence white or buff) ,000 leukocytes/µl blood; < 1% total blood volume Cells use the blood to travel; most are found in connective tissue & lymph Functions: 1. Defend against pathogens 2. Remove toxins and wastes 3. Attack abnormal/damaged cells Characteristics: 1. Amoeboid movement cytoplasm flows into cellular processes 2. Diapedesis (move out of blood): a. Margination = adhere to vessel b. Emigration = pass between endothelial cells 3. Exhibit positive chemotaxis - pathogens, damaged tissue, other WBCs 4. Phagocytosis (3 of 5) engulf pathogens and debris 26

27 19-5: 5 Types of Leukocytes a-d: Nonspecific defense e: Specific defense Fig a-e White Blood Cells 27

28 19-5 White Blood Cells: A. Neutrophils or Polymorphonuclear [PMN] Leukocytes Nonspecific defense Phagocytic 50-70% of all WBCs 2-5 lobed nucleus 12 µm diameter Granules (lysosomes) contain digestive enzymes & defensins that kill bacteria, fungi & enveloped viruses Very mobile: first at injury Life span < 10h Functions: 1. Respiratory burst: H 2 O 2 & O 2-, acts as bactericide 2. Degranulation: defensins (peptide) lyse bacteria 3. Prostaglandins: induce inflammation to stop spread of injury 4. Leukotrienes: hormones that attract other phagocytes 28

29 19-5 White Blood Cells: B. Eosinophils or Acidophils Functions: Nonspecific defense Phagocytic (secondary function) 2 4% of circulating WBCs Bilobed nucleus 12 µm diameter; 9-day life eosin dye 1. Attack antibody-coated objects (bacteria, protozoa, cell debris) 2. Defense against large parasites Excrete toxic compounds (primary function) Nitric oxide (NO) & Cytotoxic enzymes Sensitive to allergens Control inflammation with enzymes that counteract inflammatory effects of neutrophils and mast cells 29

30 19-5 White Blood Cells: C. Basophils Nonspecific defense NOT phagocytic < 1% of WBCs U shaped nucleus 8-10µm diameter Granules contain histamine dilate blood vessels heparin prevent clotting (book says this but actual function of heparin is likely defense against pathogenic infection) Life span = 9 d Similar in function to mast cells in tissue; enhance their function Functions: 1. Inflammation 2. Allergic response (via histamine) 30

31 19-5 White Blood Cells: D. Monocytes exit to tissues = macrophage Life span = several months Functions: Nonspecific defense Phagocytic 2-8% of WBCs Kidney shaped nucleus 15 µm + diameter 1. Phagocytosis: viruses and bacteria 2. Attract phagocytes 3. Attract fibroblasts for scar formation 4. Activate lymphocytes: to mount immune response Circulate 24 h, then 31

32 19-5 White Blood Cells: E. Lymphocytes Immune-Specific Response 20-30% of WBCs Large round nucleus 5-17µm diameter Migratory between blood and tissues (bidirectional) Most in lymphatic system Life span = days to lifetime Function (depends on type [3]): 1. T cells: cell-mediated immunity (attack foreign cells directly or control the activity of other lymphocytes) 2. B cells: humoral immunity (differentiate into plasma cells, which synthesize and secrete antibodies) 3. Natural Killer (NK) cells: immune surveillance or innate immunity (detect and destroy abnormal tissue; e.g., cancer) 32

33 19-5 Leukocyte Disorders & Diagnostics Changes in differential count and WBC profiles can signal infections, inflammation, and allergic reactions Leukopenia: low WBC count (penia = poverty) Leukocytosis: high WBC count (cytosis = more cells) normal infection WBCs from 7,500-11,000/µl >100,000/µl leukemia, cancerous stem cells, WBCs produced are immature and abnormal Infectious Mononucleosis (mononuclear leukocytosis): Epstein Bar virus infection causes production of excess agranulocytes (monocytes and lymphocytes) that are abnormal 33

34 19-5 White Blood Cell Production: Leukopoiesis & Lymphopoiesis All blood cells originate from hemocytoblasts, which produce: 1. Myeloid Stem Cells Differentiate into progenitor cells, which produce all WBCs except lymphocytes 2. Lymphoid Stem Cells Lymphopoiesis: the production of lymphocytes All WBCs except monocytes (and lymphocytes see below) develop fully in bone marrow Monocytes develop into macrophages in peripheral tissues 34

35 19-5 Leukopoiesis Myeloid stem cells Basophils, Eosinophils, Neutrophils and Monocytes as directed by specific colony stimulating factors (CSFs) produced by Macrophages and T cells Different CSFs (hormones) result in different cell types: 1. M-CSF stimulates monocyte production 2. G-CSF stimulates production of granulocytes (neutrophils, eosinophils, and basophils) 3. GM-CSF stimulates granulocyte and monocyte production 4. Multi-CSF accelerates production of granulocytes, monocytes, platelets, and RBCs 35

36 19-5 Lymphopoiesis Hemocytoblasts differentiates into Lymphoid Stem Cells Lymphoblast Prolymphocytes Lymphocytes Some lymphocytes are derived from lymphoid stem cells that remain in bone marrow B cells and NK cells Many lymphoid stem cells migrate to peripheral lymphoid tissues (e.g., thymus, spleen & lymph nodes) and then differentiate into mature lymphocytes Lymphoid stem cells in the thymus give rise to T cells (Discussed in much greater detail in Chapter 22 Adaptive Immune Response) 36

37 19-5 Origins & Differentiation of Blood Formed Elements Fig TPO 37

38 19-6 Blood Fractions: Platelets Flattened cell fragments involved in human clotting systems No nucleus (non-mammalian vertebrates have whole cells involved in clotting called thrombocytes) (thrombo- = clot) 2-4 µm diameter, 1 µm thick Constantly replaced, removed by spleen (phagocytized) 9 12 days in circulation 150,00-500,000 / µl of blood Thrombocytopenia abnormally low platelet count Thrombocytosis high platelet count (infection, inflammation, cancer) 1/3 are reserved (in spleen and other organs) for emergencies 38

39 19-6 Blood Fractions: Platelets Three Functions of Platelets: 1. Transport & release important clotting chemicals 2. Temporarily patch damaged vessel walls (plug) 3. Actively contract tissue after clot formation (contain actin & myosin) Platelet Production (Thrombocytopoiesis) Megakaryocytes in bone marrow breaks off membrane-enclosed cytoplasm (each megakaryocyte can produce ~4000 platelets) Induced by 1. Thrombopoietin (TPO) from kidney 2. Interleukin-6 (IL-6) stimulates platelet formation 3. Multi-CSF (promotes growth of megakaryocytes) 39

40 19-7 Hemostasis Hemostasis = cessation of bleeding Consists of three complex (and not necessarily sequential or independent) phases: 1. Vascular phase 2. Platelet phase 3. Coagulation phase 40

41 19-7 Hemostasis: 1. Vascular Phase A cut triggers vascular spasm that lasts some 30 minutes Three steps of the vascular phase 1. Endothelial cells contract: expose basal lamina to bloodstream 2. Endothelial cells release: chemical factors: ADP, tissue factor, and prostacyclin local hormones: endothelins, which stimulate smooth muscle contraction and cell division 3. Endothelial plasma membranes become sticky : seal off blood flow 41

42 19-7 Hemostasis: 2. Platelet Phase Platelet adhesion (attachment) begins within 15 s of injury Adhere to sticky endothelial surfaces, basal lamina & exposed collagen Platelet aggregation (stick together) Forms platelet plug (closes small breaks) Activated platelets release clotting cmpds: ADP platelet aggregation Thromboxane A 2 & serotonin vascular spasm Clotting factors Platelet-derived growth factor blood vessel repair Calcium ions aggregation 42

43 19-7 Hemostasis: 2. Platelet Phase Platelet aggregation must be controlled and the area restricted. Several factors limit the growth of the platelet plug: Prostacyclin: released by endothelial cells, inhibits platelet aggregation Inhibitory compounds released by WBCs entering area Circulating plasma enzymes - break down ADP at plug Negative (inhibitory) feedback: e.g., serotonin blocks ADP Development of blood clot - isolates and restricts the area 43

44 19-7 Hemostasis: 3. Coagulation Phase Begins 30 seconds or more after the injury Blood clotting (coagulation) Cascade reactions: chain reactions of enzymes and proenzymes form three pathways (extrinsic, intrinsic & common) convert circulating fibrinogen into insoluble fibrin Clotting Factors Also called procoagulants (Ca 2+ & 11 different proteins) Many of the proteins are proenzymes Required for normal clotting 44 Figure 19 12a

45 19-7 Hemostasis: 3. Coagulation Phase 45

46 19-7 Hemostasis: 3. Coagulation Pathways 1. Extrinsic pathway Begins in the vessel wall (endothelial cells), outside of bloodstream Damaged cells release Factor III or tissue factor (TF) TF + Ca 2+ + clotting factor VII = enzyme complex that activates Factor X 2. Intrinsic pathway Begins with circulating proenzymes, within bloodstream Activation of enzymes (usually Factor XII) by collagen Platelets release factors (e.g., PF 3) Series of reactions then activates Factor X 3. Common pathway Where intrinsic and extrinsic pathways converge Forms enzyme prothrombinase Converts prothrombin to thrombin Thrombin converts fibrinogen to fibrin 46

47 19-7 Hemostasis: Convergence of Coagulation Pathways Figure The Coagulation Phase of Hemostasis NOTE: Both the extrinsic and intrinsic pathways produce thrombin, but the extrinsic is shorter and faster; thus, it results in the rapid production of a small amount of thrombin that is later reinforced by additional thrombin from the intrinsic pathway. 47

48 19-7 Hemostasis: Other Considerations Positive Feedback: Production of thrombin by common pathway stimulates formation of tissue factor (TF-extrinsic) and PF-3 from platelets (intrinsic), thus forming a positive feedback loop with both the intrinsic and extrinsic pathways, respectively Clotting: Area Restriction affected by factors that either deactivate or remove factors/agents: Anticoagulants (plasma proteins) Antithrombin-III Alpha-2-macroglobulin Heparin (produced by basophils and mast cells) Protein C (activated by thrombomodulin) Prostacyclin inhibits platelet aggregation 48

49 19-7 Hemostasis: Other Considerations Dietary: Calcium Ions and Vitamin K affect almost all aspects of clotting Calcium ions (Ca 2+ ) needed for all 3 pathways (intrinsic, extrinsic and common) Vitamin K required by liver for synthesis of 4 of the clotting factors, including prothrombin Clot Retraction (occurs after clot formation) Platelets contract, pull torn area together and reduce size of damaged area (takes min) Fibrinolysis = slow process of clot dissolving Thrombin and tissue plasminogen activator (t-pa): activate plasminogen Plasminogen produces plasmin, which digests fibrin strands 49

50 19-7 Bleeding Disorders Thrombosis = clotting in undamaged vessels prevents or slows flow (intrinsic pathway) Embolus = free floating thrombosis, blocks small vessels tissue damage, heart attack, stroke Disseminated Intravascular Coagulation = widespread clotting followed by systemic bleeding, rare: complication of pregnancy, septicemia or mismatched transfusion Hemophilia = inadequate production of clotting factors Type A Factor VIII (X linked-recessive) Type B Factor IX Type C Factor XI 50

51 Chapter 19 Summary: Formed Elements in Blood 51

52 Chapter 19 Summary: Formed Elements in Blood 52

53 Chapter 19 Summary: Formed Elements in Blood 53

54 Chapter 19 Knowledge Checklist 1. Describe the components and major functions of blood. 2. Describe the composition and function of plasma. 3. List the characteristics and functions of erythrocytes, including hemoglobin, erythrocyte formation (erythropoiesis) and recycling. 4. Explain the basis of blood typing and histocompatibility. 5. Describe the structure function of white blood cells and their formation. 6. Describe the structure function of platelets. 7. Describe the mechanisms involved in blood clot formation. 54